The Ultrastructural Pathology (UP) Section provides specialized diagnostic services for cases difficult to classify with conventional methods. In addition, the UP section has a long-term commitment to: improve available diagnostic techniques for the classification of poorly differentiated solid pediatric tumors and to define prognostic factors which may lead to development of new therapeutic strategies. For this reason, the section has undertaken independent research projects (reported separately) regarding: 1) the role of growth factors in the differentiation and proliferation of pediatric tumors in vitro; 2) the identification of subgroups with p53 mutations or high mdm gene expression which may have prognostic significance and 3) the use of non-conventional diagnostic methods, such as the reverse polymerase chain reaction (RT-PCR) for more accurate characterization of certain tumors. The UP section also provides diagnostic consultative services to the Pediatric Oncology Branch (POB) at the NCI and has collaborative projects with both the POB and other investigators in the Clinical Center. Examples of clinicopathologic projects directed by the UP Section are 1) P-glycoprotein expression in Ewing's sarcoma and peripheral primitive neuroectodermal tumor (PNET) before and after treatment; 2) Proliferating cell nuclear antigen as a prognostic factor in childhood rhabdomyosarcoma; 3) Ewing's sarcoma versus PNET: does histology play a prognostic role? Examples of projects in which the UP Section has a collaborative role are: 1) differentiation of rhabdomyosarcoma cell lines with Ara-C; 2) expression of insulin-growth factor (IGF) II in rhabdomyosarcoma cells by in situ hybridization; 3) tumor regression after treatment with a monoclonal anti-IGF II antibody in a rhabdomyosarcoma nude mouse model; 4) possible induction of differentiation and/or increased levels of beta2- microglobulin after treatment of refractory neuroblastoma with tumor infiltrating lymphocytes, interferon gamma and interleukin-2; 5) evaluation of the role of cytoskeletal proteins (tubulin and vimentin) in the development of cisplatin resistance and 6) mechanisms of taxol-induced cell death in Chinese hamster V79 cells.